1. Field of the Invention
The present invention relates to a novel compound isolated from Ginkgo biloba and a method for isolating the same, and more particularly to a novel compound isolated from the Ginkgo biloba bark, which is used for the treatment of thrombus, an antiplatelet agent containing the novel compound, and a method isolating the novel compound from Ginkgo biloba. 
Thus, the novel compound discovered in the Ginkgo biloba bark according to the present invention can be considered as a very good compound for the treatment of thrombus.
2. Background of the Related Art
Ginkgo biloba is a deciduous tree belonging to the Ginkgoaceae family and contains many components found therein. As studies on flavonoids among the components have been actively conducted, the flavonoids have been found to have various physiological activities and pharmacological effects and have been frequently developed and marketed as medical drugs through clinical experiments.
Ginkgo biloba is known to contain large amounts of physiologically active substances.
The fruit of Ginkgo biloba contains phenolic compounds such as ginkgol, bilobal and ginkgolic acid, and the seed of Ginkgo biloba contains cyanogenetic glycosides, amino acids and the like. The leaf of Ginkgo biloba contains aromatic compounds, particularly phenolic compounds, flavonoid glycosides, simple flavonoids such as keampferol, quercetin, isorhamnetin and luteolin, and terpenoid compounds such as ginkgolide and bilobalid.
Studies associated with Ginkgo biloba have been mostly conducted to date on the leaf or fruit of Ginkgo biloba, but it is an object of the present invention to provide a method for isolating and purifying a novel compound from the Ginkgo biloba bark, which has been little studied.
According to data reported by Korea National Statistical Office in 2000, circulatory system diseases such as arteriosclerosis, cerebral hemorrhage, cerebral stroke and cerebral infarction are adult diseases, which are the first and second leading causes of death. Such adult diseases frequently occur in the middle- and old-age groups due to the change of dietary life styles, and external and internal environmental stresses, as society develops. The main cause of these diseases is known to be thrombus, which is recognized as a pathological phenomenon mediated by excessive platelet aggregation. Meanwhile, when blood vessels are damaged, platelets are activated by stimulation with various agonists such as collagen, thrombin and adenosine diphosphate (ADP) and are subjected to adhesion, secretion and aggregation. Such reactions are involved in hemostasis, but perform an important role in the onset circulatory system diseases, including thrombosis.
According to prior reports, when platelets are stimulated with collagen, thrombin, ADP and adrenaline, phospholipase C present in the platelet membrane is activated to degrade phosphatidylinositol 4,5-bisphosphate (PIP 2), thus producing diacyl glycerol (DG) and inositol-1,4,5-trisphosphate (IP). The produced DG activates protein C-kinase to induce the phosphorylation of 40 KDa protein and the activation of DG-lipase and MG(monoacyl glycerol)-lipase, thus inducing the release of arachidonic acid into the cytoplasm. The released arachidonic acid is converted into PGG 2 (prostaglandin prostaglandin G2)/PGH 2 (prostaglandin H2) by cyclooxygenage, from which tromboxane A 2 (TX A 2) is produced. The tromboxane is importantly involved in blood coagulation, platelet aggregation and thrombus formation.
Aspirin, which has been used as an antiplatelet agent for a long period of time, is a salicin derivative, an active ingredient from the willow bark, and shows high activity, even though it has low cost. However, clinical physicians increasingly guard against the use of aspirin due to the risk of bleeding caused by aspirin.
Currently, plavix is antiplatelet agent in the antiplatelet market, but causes side effects such as bleeding, diarrhea and abdominal pain.
Antiplatelet agents developed to date include theopylline, molsidomine, verapamil and nifedipine, which are known to inhibit the release of Ca2+ by stimulating the production of cAMP and cGMP, and nonsteroidal compounds such as aspirin, imidazole and indomethacin, which are known to act as antiplatelet agents by inhibiting the production of TXA 2. However, antiplatelet preparations, including the above-mentioned drugs, anticoagulants, and thrombolytic agents, are all purified chemical substances, and have a problem in that they cause various side effects, including excessive hemostasis, sterility and digestive disorders, when administered to the human. In other words, the drugs developed to date can prevent and treat cerebral hemorrhage, cerebral thrombosis, cerebral infarction, cardiac thrombosis, arteriosclerosis and other circulatory system diseases by suppressing the formation of thrombus, which is the main cause of these diseases, and the aggregation of platelets, which mediate the formation of thrombus. However, these medical drugs have a limitation in the use thereof due to the side effects thereof. Thus, it is urgently required to develop a natural antithrombotic agent, which is harmless to the human and are free of side effects.
As described above, the antiplatelet agents developed to date involve side effects, because these are not based on natural substances. On the other hand, the present invention relates to a novel natural compound isolated from the bark of Ginkgo biloba. In the present invention, the antiplatelet activity of the novel compound was measured.
Although blood flow improvers such as Gingkomin, Ginexin and Circulan, based on natural substances, have been marketed, these are all preparations based on components extracted from the leaf of Ginkgo biloba and can be considered as mixtures of various substances, but not single compound. On the other hand, in the present invention, a single compound isolated from Ginkgo biloba was confirmed to have antiplatelet activity.
Recently, the use of antiplatelet agents has been greatly increased due to the rapid increase of vascular diseases. Typical examples thereof are “aspirin” and “plavix”. Aspirin is an antiplatelet agent, which has been used for a very long time, and plavix is another typical antiplatelet agent, which currently leads the antiplatelet market. However, patients who received stenting to enlarge cardiovascular vessels because of angina caused by coronary arteriosclerosis (after this stenting, stent thrombosis in which thrombus is formed in the stent to block blood flow occurs) are usually administered with antiplatelet agents, aspirin and plavix. However, it was recently found that, in the case of patients in which liver enzyme CYP3A5 is not activated, aspirin and plavix have little or no effect. Thus, thrombosis therapeutic agents of various pathways should be developed for more safer treatment, and a combined therapy of antithrombotic agents having various mechanisms receives great attention, compared to a single therapy. That is, because mechanisms in which thrombus is formed are different, a need for drugs having various mechanisms exists.